The Donnan effect across the red blood cell membrane contributes to the 'chloride shift' during CO₂ transport. Which protein mediates this anion exchange and what is its clinical relevance in band 3 deficiency?

• A Glycophorin A: sialic acid-rich transmembrane protein that provides the anion exchange function
• B Aquaporin-1 (AQP1): water channel that also has CO₂ and HCO₃⁻ permeability across the RBC membrane
• C Band 3 protein (AE1/SLC4A1): Cl⁻/HCO₃⁻ anion exchanger enabling HCO₃⁻ export from RBC in tissues and import in lungs; deficiency causes hereditary spherocytosis type II and distal RTA type 1 ✓
• D RHAG (Rh-associated glycoprotein): CO₂ transporter that incidentally exchanges Cl⁻ and HCO₃⁻

Explanation

Band 3 (anion exchanger 1, AE1, encoded by SLC4A1) is the most abundant RBC membrane protein, functioning as an electroneutral Cl⁻/HCO₃⁻ exchanger. In the tissues, CO₂ diffuses into RBCs and is hydrated by carbonic anhydrase II to H⁺ + HCO₃⁻; band 3 exports HCO₃⁻ in exchange for Cl⁻ (chloride shift), greatly increasing CO₂ carrying capacity. In the lungs, the reverse occurs. Mutations in SLC4A1 affecting the RBC domain cause hereditary spherocytosis (loss of structural cytoskeletal interaction with ankyrin) and ovalocytosis; mutations in the kidney tubular (truncated) AE1 isoform cause autosomal dominant distal RTA type 1.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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